Growth factor homolog zvegf3
AssigneeZymoGenetics, Inc.
InventorsZeren Gao, Charles E. Hart, Christopher S. Piddington, Paul O. Sheppard, Kimberly E. Shoemaker, Debra G. Gilbertson, James W. West
Life of this patent
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Abstract
Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 90% identical to residues 46-163 of SEQ ID NO: 2 or residues 235-345 of SEQ ID NO: 2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.
Claims53
An isolated polypeptide of at least 15 amino acid residues comprising an epitope-bearing portion of a protein of SEQ ID NO:
- 2 or SEQ ID NO:
- 43.
An isolated polypeptide comprising a sequence of amino acids of the formula R 1x—R2y—R3z, wherein:
- R1 comprises a polypeptide of from 100 to 120 residues in length that is at least 90% identical to residues 46-163 of SEQ ID NO:
- 2, and comprises a sequence motif C[KR]Y[DNE] [WYF]X{11,15)}G[KR] [WYF] C (SEQ ID NO:
- 4) corresponding to residues 104-124 of SEQ ID NO:
- 2;
- R2 is a polypeptide at least 90% identical to residues 164-234 of SEQ ID NO:
- 2;
- R3 is a polypeptide at least 90% identical in amino acid sequence to residues 2 35-345 of SEQ ID NO:
- 2 and comprises cysteine residues at positions corresponding to residues 250, 280, 284, 296, 335, and 337 of SEQ ID NO:
- 2;
- a glycine residue at a position corresponding to residue 282 of SEQ ID NO:
- 2;
- and a sequence motif CX{18,33}CXGXCX{6,33}CX{20,40}CXC (SEQ ID NO:
- 3) corresponding to residues 250-337 of SEQ ID NO:
- 2;
- and
- each of x, y, and z is individually 0 or 1, subject to the limitations that:
- at least one of x and z is 1;
- and
- if x and z are each 1, then y is 1.
An isolated protein comprising a first polypeptide operably linked to a second polypeptide, wherein said first polypeptide comprises a sequence of amino acids of the formula R1x—R2y—R3z wherein:
- R1 comprises a polypeptide of from 100 to 120 residues in length that is at least 90% identical to residues 46-163 of SEQ ID NO:
- 2, and comprises a sequence motif C[KR]Y[DNE] [WYF]X{11,15}G[KR] [WYF]C (SEQ ID NO:
- 4) corresponding to residues 104-124 of SEQ ID NO:
- 2;
- R2 is a polypeptide at least 90% identical to residues 164-234 of SEQ ID NO:
- 2;
- R3 is a polypeptide at least 90% identical in amino acid sequence to residues 235-345 of SEQ ID NO:
- 2 and comprises cysteine residues at positions corresponding to residues 250, 280, 284, 296, 335, and 337 of SEQ ID NO:
- 2;
- a glycine residue at a position corresponding to residue 282 of SEQ ID NO:
- 2;
- and a sequence motif CX{25,33}CXGXCX{10,33}CX{20,40}CXC (SEQ ID NO:
- 3) corresponding to residues 250-337 of SEQ ID NO:
- 2;
- and
- each of x, y, and z is individually 0 or 1, subject to the limitations that:
- at least one of x and z is 1;
- and
- if x and z are each 1, then y is 1,
- and wherein said protein modulates cell proliferation, differentiation, metabolism, or migration.
An isolated polynucleotide of up to approximately 4 kb in length, wherein said polynucleotide encodes a polypeptide comprising a sequence of amino acids of the formula R1x—R2y—R3z wherein:
- R1 comprises a polypeptide of from 100 to 120 residues in length that is at least 90% identical to residues 46-163 of SEQ ID NO:
- 2, and comprises a sequence motif C[KR]Y[DNE] [WYF]X{11,15}G[KR] [WYF]C (SEQ ID NO:
- 4) corresponding to residues 104-124 of SEQ ID NO:
- 2;
- R2 is a polypeptide at least 90% identical to residues 164-234 of SEQ ID NO:
- 2;
- R3 is a polypeptide at least 90% identical in amino acid sequence to residues 235-345 of SEQ ID NO:
- 2 and comprises cysteine residues at positions corresponding to residues 250, 280, 284, 296, 335, and 337 of SEQ ID NO:
- 2;
- a glycine residue at a position corresponding to residue 282 of SEQ ID NO:
- 2;
- and a sequence motif CX{25,33}CXGXCX{10,33}CX{20,40}CXC (SEQ ID NO:
- 3) corresponding to residues 250-337 of SEQ ID NO:
- 2;
- and
- each of x, y, and z is individually 0 or 1, subject to the limitations that:
- at least one of x and z is 1;
- and
- if x and z are each 1, then y is 1.
A method for detecting a genetic abnormality in a patient, comprising:
- obtaining a genetic sample from a patient;
- incubating the genetic sample with a polynucleotide comprising at least 14 contiguous nucleotides of SEQ ID NO:
- 1 or the complement of SEQ ID NO:
- 1, under conditions wherein said polynucleotide will hybridize to complementary polynucleotide sequence, to produce a first reaction product;
- and
- comparing said first reaction product to a control reaction product, wherein a difference between said first reaction product and said control reaction product is indicative of a genetic abnormality in the patient.
A method of inhibiting zvegf3 activity in a mammal comprising administering to the mammal an effective amount of a zvegf3 antagonist.
A method of decreasing zvegf3 activity in a mammal, comprising administering to the mammal an effective amount of an antibody that specifically binds to an epitope of a polypeptide consisting of a sequence of amino acid residues selected from the group consisting of:
- residues 230-345 of SEQ ID NO:
- 2;
- residues 231-345 of SEQ ID NO:
- 2;
- residues 232-345 of SEQ ID NO:
- 2;
- residues 233-345 of SEQ ID NO:
- 2;
- residues 234-345 of SEQ ID NO:
- 2;
- residues 235-345 of SEQ ID NO:
- 2;
- residues 236-345 of SEQ ID NO:
- 2;
- residues 237-345 of SEQ ID NO:
- 2;
- residues 238-345 of SEQ ID NO:
- 2;
- residues 239-345 of SEQ ID NO:
- 2;
- and
- residues 240-345 of SEQ ID NO:
- 2.
A method of decreasing zvegf3 activity in a mammal, comprising administering to the mammal an effective amount of an antibody that specifically binds to a dimeric protein having two polypeptide chains, wherein each of said polypeptide chains consists of a sequence of amino acid residues selected from the group consisting of:
- residues 230-345 of SEQ ID NO:
- 2;
- residues 231-345 of SEQ ID NO:
- 2;
- residues 232-345 of SEQ ID NO:
- 2;
- residues 233-345 of SEQ ID NO:
- 2;
- residues 234-345 of SEQ ID NO:
- 2;
- residues 235-345 of SEQ ID NO:
- 2;
- residues 236-345 of SEQ ID NO:
- 2;
- residues 237-345 of SEQ ID NO:
- 2;
- residues 238-345 of SEQ ID NO:
- 2;
- residues 239-345 of SEQ ID NO:
- 2;
- and
- residues 240-345 of SEQ ID NO:
- 2.
Dependencies are inferred from the claim text.